We are investigating the mechanisms by which Rous sarcoma virus (RSV) replicates and induces neoplastic transformation of host cells. This work subsumes the following major projects: (1) Analyze the complexity and constitution of the viral genome. (2) Isolate nucleotide sequences which correspond to transforming genes of the virus. (3) Determine the extent of evolutionary divergence among C-type viruses of different species. (4) Elucidate the enzymatic mechanisms by which RNA-directed DNA polymerase transcribes the viral genome into DNA ("provirus"). (5) Isolate and characterize provirus DNA from acutely infected cells. (6) Describe the events which lead to the integration of provirus DNA and the synthesis of viral RNA in an infected cell. (7) Delineate the viral and cellular gene functions required for viral replication and cellular transformation. (8) Define the controls which determine the fate of a mammalian cell infected with RSV. Our techniques include: (1) enzymatic synthesis and modification of nucleic acids; (2) molecular hybridization; (3) immunoprecipitation; (4) electronmicroscopy; (5) analysis of nucleotide composition and sequence of nucleic acids; and (6) the use of conditional mutants of RSV. BIBLIOGRAPHIC REFERENCES: Stehelin, D., Guntaka, R.V., Varmus, H.E., and Bishop, J.M. Purification of DNA complementary to nucleotide sequences required for neoplastic transformation of fibroblasts by avian sarcoma viruses. J. Mol. Biol. 101:349-365, 1976. Stehelin, D., Varmus, H.E., Bishop, J.M., and Vogt, P.K. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian cells. Nature 260:170-173, 1976.